Multi-scale modeling of cardiac excitation-contraction coupling.

The diversity and quantity of currently available experimental and imaging data, including measurements of single cells, cardiac wall motion, chamber flow patterns, coronary perfusion and electrical mapping, presents a significant opportunity to improve both physiological understanding and ultimately clinical care for cardiovascular disease. However, the clinical practice of using population-based metrics derived from separate image sets often indicates contradictory treatment plans due to both a lack of integrative mechanistic understanding and inter-individual variability in pathophysiology. Thus, despite measurement advances, determining optimal treatment strategies for cardiac patients remains problematic. To exploit the full value of measurement technologies, and the combined information content they produce, requires the ability to integrate multiple types of anatomical and functional data into a consistent framework. An exciting and highly promising strategy for contributing to this integration is through the development of bio-physically based mathematical models. However, despite these advances there remains a significant translational barrier to applying and customising models to interpret specific experimental data or for human clinical application. This is because the vast majority of cardiac models are currently developed and validated using data collected from heterogeneous measurements in animal populations. These models are useful for the demonstration of proof of concept function and development of mechanistic concepts. However, there are inherent limitations to such model developments specifically with respect to quantitatively mimicking function in health and disease. Moreover, the relevance of insights gained from such models to human health remains difficult to determine. To address these issues, we present recent developments in both murine and clinically relevant human models that cover the coupling and simulation of cardiac fluid flow, mechanics, perfusion and electrical excitation. [ABSTRACT FROM AUTHOR]